{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T19:57:21Z","timestamp":1761163041602,"version":"build-2065373602"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,1,16]],"date-time":"2012-01-16T00:00:00Z","timestamp":1326672000000},"content-version":"vor","delay-in-days":2359,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2005,8]]},"abstract":"<jats:p>\n                    An 81\u2010year\u2010old woman with ischemic bowel underwent laparotomy with small\u2010bowel resection and developed septic shock. She required broad\u2010spectrum antibiotics, norepinephrine, and mechanical ventilation. The patient received drotrecogin alfa (activated) 24 \u03bcg\/kg\/hour for a total of 67.5 hours. Coagulation parameters were monitored during her therapy. Significant increases in activated partial thromboplastin time (aPTT) during infusion led to two temporary discontinuations of the drug. Coagulation parameters decreased when the drug was held and increased with each rechallenge. The patient survived the episode and was discharged on postoperative day 27. Medical records of 26 other patients who received drotrecogin alfa (activated) at our institution from November 2001\u2013August 2003 were reviewed retrospectively for coagulation parameters and bleeding rate. Of the 26 patients, nine (35%) were treatment compliant (&gt; 90% of the 96\u2010hr course). Coagulopathy and bleeding resulted in early discontinuation in four (15%) and six (23%) patients, respectively. An increase in aPTT from baseline to during infusion of drotrecogin alfa (activated) was noted in 14 patients with complete data (p=0.56). A decrease in median platelet count from baseline to during infusion was noted in the six patients who bled during therapy (p=0.01). Two of these patients had platelet counts less than 30 times 10\n                    <jats:sup>3<\/jats:sup>\n                    \/mm\n                    <jats:sup>3<\/jats:sup>\n                    during administration. Drotrecogin alfa (activated) should be considered an anticoagulant. In postmarketing reports, clinically significant bleeding occurred more frequently than was noted in a large, randomized, multicenter trial. Patients receiving drotrecogin alfa (activated) should be closely monitored for prolongation of coagulation parameters. Temporary discontinuation of the drug should be considered when international normalized ratio is greater than 3.0, platelet count is less than 15 times 10\n                    <jats:sup>3<\/jats:sup>\n                    \/mm\n                    <jats:sup>3<\/jats:sup>\n                    , and aPTT is greater than 100 seconds.\n                  <\/jats:p>","DOI":"10.1592\/phco.2005.25.8.1147","type":"journal-article","created":{"date-parts":[[2005,10,10]],"date-time":"2005-10-10T04:47:51Z","timestamp":1128919671000},"page":"1147-1150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Challenge and Rechallenge: Drotrecogin alfa (activated)\u2013Induced Prolongation of Activated Partial Thromboplastin Time in a Patient with Severe Sepsis"],"prefix":"10.1002","volume":"25","author":[{"given":"Emily E.","family":"Castelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen M.","family":"Culley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell P.","family":"Fink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200107000-00002"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022139"},{"volume-title":"Xigris (drotrecogin alfa [activated]) package insert","year":"2003","author":"Eli Lilly and Company.","key":"e_1_2_1_4_2"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/374835"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200205001-00023"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198510000-00009"},{"key":"e_1_2_1_8_2","first-page":"A122","article-title":"Incidence of coagulopathy, bleeding and mortality in drotrecogin alfa (activated)\u2010treated patients [abstr]","volume":"31","author":"Castelli EE","year":"2003","journal-title":"Crit Care Med"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441001"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441009"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200301001-00012"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc1911"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200212001-00349"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200212001-00351"},{"issue":"12","key":"e_1_2_1_15_2","first-page":"A104","article-title":"Clinical outcomes and adverse effects of patients treated with drotrecogin alfa [abstr]","volume":"30","author":"Nguyen NQ","year":"2002","journal-title":"Crit Care Med"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200212001-00355"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH02-11-0270"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-003-1781-4"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.2005.25.8.1147","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.2005.25.8.1147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:14:58Z","timestamp":1761066898000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.2005.25.8.1147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2005,8]]}},"alternative-id":["10.1592\/phco.2005.25.8.1147"],"URL":"https:\/\/doi.org\/10.1592\/phco.2005.25.8.1147","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"type":"print","value":"0277-0008"},{"type":"electronic","value":"1875-9114"}],"subject":[],"published":{"date-parts":[[2005,8]]},"assertion":[{"value":"2012-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}